High-frequency oscillations in circulating amylin concentrations in healthy humans

Amylin is stored in the pancreatic beta-cell granules and cosecreted with i nsulin in response to nutrient stimuli. To gain further insight into contro l of hormonal release in beta-cell physiology, we examined whether amylin, like insulin, circulates in a high-frequency oscillatory pattern, and if it does, to compare the secretory patterns of the two hormones. Eight overnig ht-fasted healthy individuals were studied during intravenous glucose infus ion (2.0 mg.kg(-1).min(-1)). Blood was collected every minute for 90 min an d analyzed in triplicate for amylin, total amylin immunoreactivity (TAI), a nd insulin. Mean plasma concentrations of amylin (nonglycosylated), TAI (no nglycosylated plus glycosylated), insulin, and glucose were 2.77 +/- 1.21 p mol/l, 7.60 +/- 1.73 pmol/l, 50.4 +/- 17.5 pmol/l, and 5.9 +/- 0.3 mmol/l, respectively. The 90-min time series of amylin, TAI, and insulin were analy zed for periodicity (by spectral analysis, autocorrelation analysis, and de convolution analysis) and regularity [by approximate entropy (ApEn)]. Signi ficant spectral density peaks were demonstrated by a random shuffling techn ique in 7 (out of 7), 8 (out of 8), and 8 (out of 8) time series, respectiv ely, whereas autocorrelation analysis revealed significant pulsatility in 5 (out of 7), 7 (out of 8), and 5 (out of 8), respectively. The dominant per iodicity of oscillations determined by spectral analysis was 4.6 +/- 0.3, 4 .6 +/- 0.4, and 6.5 +/- 1.1 min/pulse, respectively (amylin vs. insulin, P = 0.017, TAI vs. insulin, P = 0.018). By deconvolution analysis, amylin and insulin periodicities were, respectively, 6.3 +/- 1.0 and 5.5 +/- 0.6 min. By application of the regularity statistic, ApEn, 6 (out of 7), 7 (out of 8), and 6 (out of 8), respectively, were found to be significantly differen t from random. In conclusion, like several other hormones, circulating amyl in concentrations exhibit oscillations in the secretory patterns for nongly cosylated as well as glycosylated forms. Whether the high-frequency pulsati le release of amylin is disturbed in diabetes is not known.